Mechanisms of airspace enlargement in pulmonary emphysema. The traditional inflammatory cell hypothesis stipulates that cigarette smoke results in accumulation of inflammatory cells that release proteinases (neutrophil elastase [NE], macrophage elastase [MMP-12], and cysteine proteinases) disrupting extracellular matrix and basement membrane. Loss of cell-matrix attachment leads to apoptosis with loss of the entire alveolar unit. Proposed here is an alternative hypothesis whereby cell death is the primary stimulus with subsequent loss of matrix components resulting in loss of the alveolar unit.